Highlights from Spectrum Pharma $SPPI investor event (excerpts c/o SeekingAlpha) with updated commentary on every major development / commercial product. For archival purposes (June 2013)
The first part of my summary of news and notes from Spectrum Pharma's year-end earnings conference call focused on apaziquone, the bladder cancer drug that missed in phase 3 and was recently returned by partner Allergan. You can read SPPI Part 1 here.
Part 2 will cover other highlights, particularly regarding Fusilev and Zevalin. Of course all of these comments should be taken with a grain of salt given the bombshell press release SPPI released a couple weeks later. In some cases the change in commentary in such a short period of time is very difficult to reconcile.
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Spectrum Pharma SPPI recently held their fourth-quarter and full-year 2012 earnings call. Topics of discussion included each of the marketed or late-stage cancer drugs: FUSILEV, ZEVALIN, FOLOTYN, belinostat, and apaziquone.
In this Part 1 post, I am including highlights from the SPPI and (former) partner Allergan AGN's earnings calls regarding apaziquone.
(continue reading full post for details)
TopoTarget (partner of Spectrum Pharma $SPPI) conference call notes - belinostat in CUP trial results
TopoTarget is a European biotech company that licensed the histone deacetylase (HDAC) inhibitor belinostat to Spectrum Pharma $SPPI. In June 2012 Topo released top-line data for the clinical trial in cancer of unknown primary (CUP) - belinostat failed to achieve the primary endpoint of an increase in progression-free survival (PFS). A secondary endpoint of objective response rate (ORR) was positive and statistically significant.
The company then held a conference call to explain the results and justify to shareholders why they shouldn't view this as a failure. They even went so far as to release a further press release in August 2012 with some new data-mining. This sort of behavior is typical of small biotech companies heavily reliant on the fate of a single drug, and diligent biotech investors must recognize this and not invest in a company advancing a drug out of necessity or convenience vs. actual clinical and commercial potential.
My notes from the conference call continue below the jump.
Continue reading below the jump for extensive notes from the 3q-2011 Spectrum Pharma SPPI earnings call regarding each clinical and commercial product and future directions.
Spectrum Pharma $SPPI will present data at the 2012 ASCO meeting in June on two cancer programs: belinostat and ZEVALIN. Expand the full post for the complete abstarcts.
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A commentary entitled "The Shortage of Essential Chemotherapy Drugs in the United States" by Drs Mandy Gatesman and Thomas Smith appeared in the New England Journal of Medicine on October 31, 2011.
There are some interesting takeaways from this piece, including some perspective on the ongoing market conditions between Spectrum Pharma's (SPPI) Fusilev (levoleucovorin) and generic leucovorin.
"In a survey from the Institute for Safe Medication Practices, 25% of clinicians indicated that an error had occurred at their site because of drug shortages. Many of these errors were attributed to inexperience with alternative products — for instance, incorrect administration of levoleucovorin (Fusilev) when used as a substitute for leucovorin or use of a 1000-mg vial of cytarabine instead of the usual 500-mg one, resulting in an overdose"
"The main cause of drug shortages is economic. If manufacturers don't make enough profit, they won't make generic drugs. There have been some manufacturing problems, but manufacturers are not required to report any reasons or timetable for discontinuing a product. Contamination and shortages of raw materials probably account for less than 10% of the shortages. In addition, if a brand-name drug with a higher profit margin is available, a manufacturer may stop producing its generic. For instance, leucovorin has been available from several manufacturers since 1952. In 2008, levoleucovorin, the active l-isomer of leucovorin, was approved by the Food and Drug Administration. It was reportedly no more effective than leucovorin and 58 times as expensive, but its use grew rapidly. Eight months later, a widespread shortage of leucovorin was reported."
Generic leucovorin costs $32 per dose, whereas Fusilev costs $1284 - these extreme price differences also exist between other older generics (paclitaxel and doxyrubicin also cited) and their brand name competitors. This cost disparity contributes to the lack of commitment to generics in another way - the way that oncology drugs are purchased by doctors and then reimbursed by the healthcare payers. These rules were changed in 2003 to be a fixed 6% above cost - this provides incentive to prescribe the higher priced drugs since they make more money for the oncology practice.
The article goes on to discuss various reform possibilities that would address this and other issues in the healthcare system - I'll leave those discussions for another day!
This issue also was raised on a recent Sanofi conference call - speaks to the possibility that the generic leucovorin suppliers may not have much incentive to quickly resolve production delays. This would of course be a positive for SPPI's continued strong Fusilev sales.
SNY call quotes:
"So the issue in the U.S. is that there is an extreme shortage of certain older generic injectible drugs, principally. This appears to be a result of the fact that, as the FDA is busy becoming more demanding on inspections throughout the industry, including the generic sector. We all know that you have to continuously invest in injectible manufacturing technology. This is some of the most sophisticated and demanding production in the biopharmaceutical space. And it appears that some companies are finding that the upgrades to manufacturing are not really justified, given the really low margins on some products. So a number of companies appear to have gone out of stock.
I encountered this in meetings with the FDA in the U.S. I was actually surprised to learn that this isn’t really a short-term issue, this has been going on for a minimum of a year. So – and you’ve seen that the president has actually asked the FDA – it’s the first, I think, executive order that president of the United States has given the FDA in over 40 years – to actually look actively at how the FDA can facilitate others to come into the market and supply some of these products. Some of these are Sanofi products that we produce in Europe and around the world. And so we have made an offer that we could potentially – if there was a regulatory path, that we could potentially provide product. But at this stage, there’s nothing concrete to report and not clear whether the FDA will in fact provide that regulatory pathway."
The efficacy of varying concentrations of intravesical apaziquone on murine bladder cancer in an animal model
Introduction and Objectives:
Apaziquone is a novel bioreductive alkylating agent in development for intravesical therapy of nonmuscle invasive bladder cancer. The standard dose of apaziquone in all ongoing clinical studies is 4 mg/ 40 mL (0.1mg/mL). The objective of this study was to test the efficacy of varying concentrations of apaziquone versus placebo in an animal model of bladder cancer.
A total of 1x105 MB49 cells were instilled into the bladder of C57BL/6 mice after electrocauterization to establish the tumor model. Mice bearing orthotopic tumors were administered varying concentrations of apaziquone (0.05, 0.1, 0.4, and 0.8 mg/mL) or placebo (0.85% saline) via intravesical instillation (0.1 mL) one week after tumor implantation. Instillations were continued once a week for 4 weeks. Tumor incidence, overall and median survival is reported.
At the end of the observation period (80 days), all animals in the control (0.85% saline) and 0.05 mg/mL groups had died (fig. 1). The median survival of mice receiving apaziquone at concentrations of 0.1 mg/mL (42.5 days); 0.4 mg/mL (40.5 days) and 0.8 mg/mL (49 days) was longer than that of mice treated with 0.05 mg/mL (30 days) and 0.85% saline (27 days). Statistically significant differences in survival were observed in control vs apaziquone-treated groups [0.1 mg/ml(P < 0.05); 0.4 mg/mL(P < 0.01); 0.8 mg/mL (P < 0.01)], and in the low concentration (0.05 mg/mL) vs 0.1 mg/mL (P < 0.05), 0.4 mg/mL (P < 0.01) and 0.8 mg/mL (P < 0.01), respectively.
The median survival of the 0.1, 0.4 and 0.8 mg/mL treated groups did not differ, but 33.3% in the 0.1 mg/mL cohort, and 14.3% in the 0.4 mg/mL cohort were long-term survivors (>80 days). All other animals (n = 37) had died of cancer by the end of the observation period. Three mice did not survive anesthesia. At necropsy all mice had advanced local disease with deep invasion of the muscularis propria, and usually with multiple lung metastases.
Apaziquone at the 0.1 mg/mL concentration demonstrates excellent antitumor activity compared to placebo or 0.05 mg/mL solutions. In this model there was no significant difference in the median survival between 0.1 mg/mL and higher concentrations of apaziquone (0.4 and 0.8 mg/mL) supporting continued development with the current clinical dose (0.1mg/mL).